Failure of the beige genotype (bg/bg) to alter the morphology of uterine granulated metrial gland cells

1989 ◽  
Vol 47 ◽  
pp. 908-909
Author(s):  
S. Yamashiro ◽  
T. Bast ◽  
B.A. Croy
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Severe Combined Immunodeficiency ◽  
Cell Lineage ◽  
Outer Zone ◽  
Late Gestation ◽  
Secretory Cells ◽  
Morphological Marker ◽  
Metrial Gland ◽  
Chediak Higashi Syndrome

Granulated metrial gland (GMG) cells are bone marrow-derived cells that differentiate from small, lymphoid-like precursor cells to become large granulated lymphocyte-like cells during murine pregnancy. The cells are localized in the mesometrial triangle and decidua basalis by day 8 of gestation, migrate through the mature placenta and become degenerate in late gestation. The function and lineage of GMG cells are unknown but some experiments suggest that they may be NK cells. Mice of genotype scid/scid have a severe combined immunodeficiency and lack functional B and T lymphocytes. However, both NK cells and GMG cells have been demonstrated in scid/scid mice. To determine whether these two populations are of the same lineage we developed mice of genotype scid/scid,bg/bg, providing a morphological marker, the Chediak-Higashi giant granule phenotype, to NK cells and have asked whether GMG cells share this lymphomyeloid phenotype.Small pieces of uterine tissues including endo-myometriura from scid/scid and scid/scid.bg/bg at 12th day of gestation were routinely processed for transmission electron microscopy. Ultrastrueturally, large, oval GMG cells were easily recognizable in both scid/scid (Fig. 1) and scid/bg (Fig. 2) uteri due to their cytological features. Nuclei of these cells contained fine chromatin and prominent nucleolus. The cytoplasm was abundant and contained large amounts of free ribosomes and granular endoplasmic reticulum, well developed Golgi complex and prominent membrane-bound granules of variable shapes and sizes (Figs. 1 & 2). The granules were generally oval to spherical and consisted of two zones. The central homogeneous zone, comprising of about 90% of the granule, was less electron opaque than crescent-shaped, outer zone. The crescent-shaped zone contained minute vacuoles and particles (Figs. 1 & 2 insets). The GMG cells exhibited features commonly seen in secretory cells, which were consistent with previous reports. The inclusion characteristic in Chediak-Higashi syndrome was not observed in the GMG cells of the scid/scid.bg/bg (Fig. 2). These observations are suggestive of GMG cells not sharing the NK cell lineage pathway.

scholarly journals Redefining interferon-producing killer dendritic cells as a novel intermediate in NK-cell differentiation

Blood ◽  
2012 ◽  
Vol 119 (19) ◽  
pp. 4349-4357 ◽  
Author(s):  
Fanny Guimont-Desrochers ◽  
Geneviève Boucher ◽  
Zhongjun Dong ◽  
Martine Dupuis ◽  
André Veillette ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Nk Cells ◽  
Adoptive Transfer ◽  
Nk Cell ◽  
Cell Lineage ◽  
Current View ◽  
Antitumoral Activity ◽  
Nk Cell Differentiation ◽  
A Cell

Abstract The cell lineage origin of IFN-producing killer dendritic cells (IKDCs), which exhibit prominent antitumoral activity, has been subject to debate. Although IKDCs were first described as a cell type exhibiting both plasmacytoid DC and natural killer (NK) cell properties, the current view reflects that IKDCs merely represent activated NK cells expressing B220, which were thus renamed B220+ NK cells. Herein, we further investigate the lineage relation of B220+ NK cells with regard to other NK-cell subsets. We surprisingly find that, after adoptive transfer, B220− NK cells did not acquire B220 expression, even in the presence of potent activating stimuli. These findings strongly argue against the concept that B220+ NK cells are activated NK cells. Moreover, we unequivocally show that B220+ NK cells are highly proliferative and differentiate into mature NK cells after in vivo adoptive transfer. Additional phenotypic, functional, and transcriptional characterizations further define B220+ NK cells as immediate precursors to mature NK cells. The characterization of these novel attributes to B220+ NK cells will guide the identification of their ortholog in humans, contributing to the design of potent cancer immunotherapies.

Evidence for Killing of Mesenchymal Stem Cells (MSC) by Autologous Natural Killer Lymphocytes.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1290-1290 ◽  
Author(s):  
Alessandro Poggi ◽  
Anna-Maria Massaro ◽  
Simone Negrini ◽  
Ivana Pierri ◽  
Manuela Balocco ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
T Lymphocytes ◽  
Nk Cells ◽  
Natural Killer ◽  
Viral Infections ◽  
Nk Cell ◽  
Cell Lineage ◽  
Culture Conditions ◽  
Inhibitory Receptors

Abstract In this study, Mesenchymal Stem Cells (MSC) were obtained from bone marrow of 10 patients suffering from acute myeloid leukemia (AML), six M0/1 two M2, and two M5 (according to the FAB classification), 8 out of 10 in post-chemotherapy complete remission. These cells differentiated into adipocytes or osteoblasts under appropriate culture conditions. MSC were CD44+, CD73a+ CD73b+ CD105+, beta1 integrin+, ICAM1+, HLA-I+, HLA-II+ (variable proportions), CD45−, CD31−, CD34− and they constitutively expressed the stress-inducible MHC-related molecules MIC-A and the UL16 (induced at the surface of cells infected by cytomegalovirus) binding protein ULBP3. These molecules are reported ligands for the NKG2D receptor expressed by natural killer (NK) and CD8+ T lymphocytes, effector cells that are thought to play a role in host defence against tumors. NK cells have also been shown to regulate normal differentiation of hemopoietic precursor into the myeloid or lymphoid cell lineage. Moreover, it has been stated that NK cells are not able to damage autologous cells, as they receive negative signals through inhibitory receptors, including killer Ig-like receptors (KIR) or C-type lectin inhibitory receptors (CLIR), which bind to HLA-I discrete alleles. Surprisingly, we found that autologous IL2-activated, but not freshly isolated, NK cells lysed MSC, while T lymphocytes did not kill self or non-self MSC. Binding of ICAM-1 expressed by MSC to its receptor, the integrin LFA-1, expressed by NK cells plays a key role in MSC/NK interaction. More importantly, NKG2D/MICA and/or NKG2D/ULBP3 engagement is responsible for the delivery of lethal hit. Conversely, it appears that HLA-I molecules do not protect MSC from NK cell-mediated injury. Taken together, these data suggest that NK cells, when activated as it may occur during the first response to viral infections, are able to eliminate MSC, thus altering the normal interactions with hemopoietic precursors and possibly affecting their differentiation. This mechanism might also contribute to the development of aberrant precursors as observed in acute leukaemias.

scholarly journals Natural killer (NK) cell response to virus infections in mice with severe combined immunodeficiency. The stimulation of NK cells and the NK cell-dependent control of virus infections occur independently of T and B cell function.

1991 ◽  
Vol 173 (5) ◽  
pp. 1053-1063 ◽  
Author(s):  
R M Welsh ◽  
J O Brubaker ◽  
M Vargas-Cortes ◽  
C L O'Donnell
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Cell Response ◽  
Nk Cell ◽  
Severe Combined Immunodeficiency ◽  
Scid Mice ◽  
Combined Immunodeficiency ◽  
Virus Infections ◽  
Mcmv Infection

The activation, proliferation, and antiviral properties of natural killer (NK) cells were examined in severe combined immunodeficiency (SCID) mice to determine the influence of mature T or B cells on virus-induced NK cell functions and to more conclusively determine the antiviral properties of prototypical CD3- NK cells. NK cells were activated to high levels of cytotoxicity 3 d after infection of mice with lymphocytic choriomeningitis virus (LCMV) or murine cytomegalovirus (MCMV). Analyses of spleen leukocytes from LCMV-infected mice by a variety of techniques indicated that the NK cells proliferated and increased in number during infection. Propidium iodide staining of the DNA of cycling cells revealed that the great majority of proliferating spleen leukocytes 3 d after LCMV infection was of the NK cell phenotype (CD3-, Ig-, Mac-1+, CZ1+, 50% Thy-1+), in contrast to uninfected mice, whose proliferating cells were predominantly of other lineages. Analyses of the NK cell responses over a 2 wk period in control CB17 mice infected with MCMV indicated a sharp rise in serum interferon (IFN) and spleen NK cell activity early (days 3-5) in infection, followed by sharp declines at later stages. In SCID mice the IFN levels continued to rise over a 10-d period, whereas the NK cell response peaked on day 3-5 and gradually tapered. In contrast to the immunocompetent CB17 mice, SCID mice did not clear the MCMV infection and eventually succumbed. SCID mice, again in contrast to immunocompetent CB17 mice, also failed to clear infections with LCMV and Pichinde virus (PV); these mice, infected as adults, did not die but instead developed long-term persistent infections. Depletion of the NK cells in vivo with antiserum to asialo GM1 rendered both SCID and CB17 control mice much more sensitive to MCMV infection, as shown by titers of virus in organs and by survival curves. In contrast, similar depletions of NK cells did not enhance the titers of the NK cell-resistant virus, LCMV. Two variants of PV, one sensitive to NK cells and the other selected for resistance to NK cells by in vivo passage, were also tested in NK cell-depleted SCID mice. The NK-sensitive PV replicated to higher titers in NK cell-depleted SCID mice, whereas the titers of the NK cell-resistant PV were the same, whether or not the mice had NK cells. These experiments support the concept that CD3- prototypical NK cells mediate resistance to NK cell-sensitive viruses via a mechanism independent of antiviral or "natural" antibody.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals NK Cells from RAG- or DCLRE1C-Deficient Patients Inhibit HCMV

2019 ◽  
Vol 7 (11) ◽  
pp. 546 ◽  
Author(s):  
Zeguang Wu ◽  
Narmadha Subramanian ◽  
Eva-Maria Jacobsen ◽  
Kerstin Laib Sampaio ◽  
Johannes van der Merwe ◽  
...  
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Acute Infection ◽  
Severe Combined Immunodeficiency ◽  
Cell Subset ◽  
Virus Infections ◽  
Recombination Activating Genes ◽  
New Findings ◽  
Critical Components

The recombination-activating genes (RAGs) and the DNA cross-link repair 1C gene (DCLRE1C) encode the enzymes RAG1, RAG2 and Artemis. They are critical components of the V(D)J recombination machinery. V(D)J recombination is well known as a prerequisite for the development and antigen diversity of T and B cells. New findings suggested that RAG deficiency impacts the cellular fitness and function of murine NK cells. It is not known whether NK cells from severe combined immunodeficiency (SCID) patients with defective RAGs or DCLRE1C (RAGs−/DCLRE1C−-NK) are active against virus infections. Here, we evaluated the anti-HCMV activity of RAGs−/DCLRE1C−-NK cells. NK cells from six SCID patients were functional in inhibiting HCMV transmission between cells in vitro. We also investigated the expansion of HCMV-induced NK cell subset in the RAG- or DCLRE1C-deficient patients. A dynamic expansion of NKG2C+ NK cells in one RAG-2-deficient patient was observed post HCMV acute infection. Our study firstly reveals the antiviral activity of human RAGs−/ DCLRE1C−-NK cells.

scholarly journals CD94 1A transcripts characterize lymphoblastic lymphoma/leukemia of immature natural killer cell origin with distinct clinical features

Blood ◽  
2005 ◽  
Vol 106 (10) ◽  
pp. 3567-3574 ◽  
Author(s):  
Chung-Wu Lin ◽  
Ting-Yun Liu ◽  
Shee-Uan Chen ◽  
Kun-Teng Wang ◽  
L. Jeffrey Medeiros ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Cell Lineage ◽  
Lymphoid Cells ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Gene Rearrangements

AbstractMost lymphoblastic lymphomas (LBLs) are regarded as neoplasms of immature T cells because they express cytoplasmic CD3 and frequently carry T-cell receptor (TCR) gene rearrangements. Immature natural killer (NK) and T cells, however, have a common bipotent T/NK-cell precursor in the thymus, and NK cells also express cytoplasmic CD3. Thus, some LBLs could arise from immature NK cells. Mature NK cells express 2 CD94 transcripts: 1A, induced by interleukin 15 (IL-15), and 1B constitutively. Because immature NK cells require IL-15 for development, CD94 1A transcripts could be a marker of NK-LBL. To test this hypothesis, we used laser capture microdissection to isolate IL-15 receptor α+ lymphoid cells from the thymus and showed that these cells contained CD94 1A transcripts. We then assessed for CD94 transcripts in 21 cases of LBL that were cytoplasmic CD3+, nuclear terminal deoxynucleotidyl transferase positive (TdT+), and CD56-, consistent with either the T-cell or NK-cell lineage. We found that 7 LBLs expressed CD94 1A transcripts without TCR gene rearrangements, suggesting NK-cell lineage. Patients with NK-LBL were younger than patients with T-LBL (15 years versus 33 years; P = .11) and had a better 2-year survival (100% versus 27%; P < .01). These results improve the current classification of LBL and contribute to our understanding of NK-cell differentiation.

Identification of the earliest NK-cell precursor in the mouse BM

Blood ◽  
2011 ◽  
Vol 117 (20) ◽  
pp. 5449-5452 ◽  
Author(s):  
Sebastian Carotta ◽  
Swee Heng Milon Pang ◽  
Stephen L. Nutt ◽  
Gabrielle T. Belz
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Cell Lineage ◽  
In Vitro Differentiation ◽  
Cell Precursor ◽  
Factor Inhibitor ◽  
Nk Cell Differentiation ◽  
The Common ◽  
Inhibitor Of Dna Binding

Abstract Natural killer (NK) cells are generated in the bone marrow (BM) from lymphoid progenitors. Although several different maturation states of committed NK cells have been described, the initial stages of NK-cell differentiation from the common lymphoid progenitor are not well understood. Here we describe the identification of the earliest committed NK-cell precursors in the BM. These precursors, termed pre-pro NK cells, lack the expression of most canonical NK cell–specific surface markers but express the transcription factor inhibitor of DNA binding 2 and high levels of the IL-7 receptor. In vitro differentiation studies demonstrate that pre-pro NK cells are committed to NK-cell lineage and appear to be upstream of the previously identified NK-cell progenitor population.

scholarly journals miR-150 regulates the development of NK and iNKT cells

2011 ◽  
Vol 208 (13) ◽  
pp. 2717-2731 ◽  
Author(s):  
Natalie A. Bezman ◽  
Tirtha Chakraborty ◽  
Timothy Bender ◽  
Lewis L. Lanier
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Substantial Reduction ◽  
Cell Lineage ◽  
Cell Development ◽  
Inkt Cell ◽  
Intrinsic Defect ◽  
Inkt Cells ◽  
Factor C ◽  
And Function

Natural killer (NK) and invariant NK T (iNKT) cells are critical in host defense against pathogens and for the initiation of adaptive immune responses. miRNAs play important roles in NK and iNKT cell development, maturation, and function, but the roles of specific miRNAs are unclear. We show that modulation of miR-150 expression levels has a differential effect on NK and iNKT cell development. Mice with a targeted deletion of miR-150 have an impaired, cell lineage–intrinsic defect in their ability to generate mature NK cells. Conversely, a gain-of-function miR-150 transgene promotes the development of NK cells, which display a more mature phenotype and are more responsive to activation. In contrast, overexpression of miR-150 results in a substantial reduction of iNKT cells in the thymus and in the peripheral lymphoid organs. The transcription factor c-Myb has been shown to be a direct target of miR-150. Our finding of increased NK cell and decreased iNKT cell frequencies in Myb heterozygous bone marrow chimeras suggests that miR-150 differentially controls the development of NK and iNKT cell lineages by targeting c-Myb.

scholarly journals Engraftment of Bone Marrow from Severe Combined Immunodeficient (SCID) Mice Reverses the Reproductive Deficits in Natural Killer Cell–deficient tgε26 Mice

1998 ◽  
Vol 187 (2) ◽  
pp. 217-223 ◽  
Author(s):  
Marie-Josée Guimond ◽  
Baoping Wang ◽  
B. Anne Croy
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Fetal Loss ◽  
Vascular Pathology ◽  
Metrial Gland ◽  
Unk Cell

A large, transient population of natural killer (NK) cells appears in the murine uterine mesometrial triangle during pregnancy. Depletion of uterine (u) NK cells, recently achieved using gene-ablated and transgenic mice, results in pathology. Pregnancies from matings of homozygous NK and T cell–deficient tgε26 mice have <1% of normal uNK cell frequency, no development of an implantation site–associated metrial gland, and an edematous decidua with vascular pathology that includes abnormally high vessel walls/lumens ratios. Fetal loss of 64% occurs midgestation and placentae are small. None of these features are seen in pregnant T cell–deficient mice. To confirm the role of the NK cell deficiency in these reproductive deficits, transplantation of tgε26 females was undertaken using bone marrow from B and T cell–deficient scid/scid donors. Engrafted pregnant females have restoration of the uNK cell population, induced metrial gland differentiation, reduced anomalies in the decidua and decidual blood vessels, increased placental sizes, and restoration of fetal viability at all gestational days studied (days 10, 12, and 14). Thus, uNK cells appear to have critical functions in pregnancy that promote decidual health, the appropriate vascularization of implantation sites, and placental size.

scholarly journals Inhibitory effect of granulocyte-macrophage colony-stimulating factor therapy on the generation of natural killer cells

Blood ◽  
1991 ◽  
Vol 78 (12) ◽  
pp. 3241-3247 ◽  
Author(s):  
A Shibuya ◽  
K Taguchi ◽  
H Kojima ◽  
T Abe
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Cell Lineage ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract We investigated the effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) therapy on the natural killer (NK) cell lineage in patients with aplastic anemia and myelodysplastic syndrome. Selected bone marrow (BM) cells were prepared by the elimination of nylon wool-adherent cells and mature T and NK cells from BM cells. The frequency of BM NK progenitors relative to BM cells selected was significantly decreased 4 weeks after the start of rhGM- CSF therapy (P less than .01), while the peripheral blood NK cell count and NK activity were also significantly decreased (P less than .05). A return to the pretreatment levels was seen 4 weeks after the cessation of treatment in all cases. No suppressive effect was noted in the patients who received rhG-CSF therapy. These results suggest that rhGM- CSF therapy suppresses the generation of NK cells from human BM NK progenitors.

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